Gas transport during in vitro and in vivo preclinical testing of inert gas therapies

New gas therapies using inert gases such as xenon and argon are being studied, which require in vitro and in vivo preclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze an in vitro exper...

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Bibliographic Details
Published inMedical gas research Vol. 6; no. 1; pp. 14 - 19
Main Authors Katz, Ira, Palgen, Marc, Murdock, Jacqueline, Martin, Andrew, Farjot, Géraldine, Caillibotte, Georges
Format Journal Article
LanguageEnglish
Published India Wolters Kluwer - Medknow Publications 01.01.2016
Medknow Publications and Media Pvt. Ltd
Medknow Publications & Media Pvt. Ltd
Medknow Publications & Media Pvt Ltd
Subjects
Animals
Carbon dioxide
Dose-response relationship
Experiments
Gas flow
Gases
Medical gases
Medical research
Metabolism
Property values
Respiration
Storage
Transportation
Ventilation
organoprotection
neuroprotection
pharmacokinetics
argon
noble gases
xenon
rats
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Summary:New gas therapies using inert gases such as xenon and argon are being studied, which require in vitro and in vivo preclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze an in vitro experiment for gas transport to a 96 cell well plate and an in vivo delivery to a small animal chamber, where the key processes considered are the wash-in of test gas into an apparatus dead volume, the diffusion of test gas through the liquid media in a well of a cell test plate, and the pharmacokinetics in a rat. In the case of small animals in a chamber, the key variable controlling the kinetics is the chamber wash-in time constant that is a function of the chamber volume and the gas flow rate. For cells covered by a liquid media the diffusion of gas through the liquid media is the dominant mechanism, such that liquid depth and the gas diffusion constant are the key parameters. The key message from these analyses is that the transport of gas during preclinical experiments can be important in determining the true dose as experienced at the site of action in an animal or to a cell.
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IK conceived the study, analyzed the results and drafted the manuscript; JM developed the pharmacokinetics model and read the manuscript; MP further developed the pharmacokinetics model, ran the simulations and organized the data, and read the manuscript; ARM helped develop the diffusion model and edited the manuscript, and designed the original in vitro and in vivo exposures upon which the analysis is based; GF read the manuscript, and GC helped to conceive the study and read the manuscript. All authors approved the final version of the paper.
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ISSN:2045-9912
2045-9912
DOI:10.4103/2045-9912.179342